Heavy Metal Toxicity

Prepared by Dr. Sahar EL.Kharraz, MSc, MD

Heavy Metal Toxicity
• Heavy metals" are chemical elements with a specific gravity at least 5
times that of water.

• Heavy metal toxicity is an excessive build-up of metals in the body.

• The most common heavy metals that humans are exposed to are
aluminum, arsenic, lead, and mercury.

• Most metalic have metalic taste if ingested except arsenic which is

tasteless.

• Most metals cause diarrhea except lead which causes constipation.

• The antidotes are called chelators

They are general protoplassmic toxins with some organ
:selectivity like

Lead/Mercury Nephrotoxicity/Neurotoxicity

Arsenic GIT upset/ Systemic Involvement

Antimony Cardio toxicity

Thalium CNS/eye/endocrine/renal

Phosphorous Hepatotoxic

Beryillium Pulmonary/skin
Common Causes
• Acute exposure can occur as a result of:

• * Receiving vaccinations that contain (mercury preservative)

• * Mishandled metals at a job site
• * Chemical and heavy metal spills–even from a broken mercury
thermometer
Chronic exposure happens over a period of time, and
includes:
* Having mercury amalgams (“silver fillings”) in teeth
* industrial inhalation of fumes
* Eating foods (such as contaminated fish) that contain
high levels of heavy metals
* Living near a landfill
* Working in an environment where exposure is
prevalent, such as at a dentist’s office where amalgam is
used to fill cavities
Symptom of Heavy Metal
Lead poisoning
• Lead is the most common metallic poison.
• It occurs in organic & inorganic forms.

• Lead poisoning occurs when lead builds up in the body, often

over a period of months or years.
• Even small amounts of lead can cause serious health problems.

• Absorption of ingested lead in children is much more than in

adults.

• About 50% of ingested dose is absorbed in children while only

10% in adults.
Sources of lead
• Lead is everywhere, including dirt,
• dust, new toys, and old house paint.

• •Occupational exposure: Plumbing, pipes, faucets & glass

manufacturers.

• • Soil: Lead is more common in soil near highways and houses.

• •Water: drinking water from lead pipes or storage tanks.

• Lead-containing products: Some cosmetics

• & folk medicine, Lead bullets, Storage batteries.
Pathophysiology
• Exposure occurs through inhalation, ingestion & from skin
contact.

• inorganic lead found in paint, food, and most lead-containing.

• The main sources of absorption of inorganic lead are from

ingestion and inhalation.

• The main body compartments that store lead are the blood, soft
tissues, and bone; the half-life of lead in these tissues is
measured in weeks for blood, months for soft tissues, and years
for bone.

• Lead in the bones, teeth, hair, and nails is bound tightly.

 Pathophysiology
• The major mechanism of lead toxicity is due to increased generation of reactive oxygen
species (ROS) and interference with generation of antioxidants.

• Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet
oxygen.

• ROS are stabilized by glutathione in the body.

• Glutathione is antioxidant defense mechanism.

• Lead inactivates glutathione by binding to GSH’s sulfhydryl group, which causes GSH
replenishment to become inefficient, thereby increasing oxidative stress.

• Lead also interferes with the activity of other antioxidant enzymes including superoxide
dismutase and catalase.

• The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation.

• Lead blocks the activity of 5-aminolevulinic acid dehydratase and leads to hemoglobin
oxidation, which along with the lipid peroxidation can result in red cell hemolysis.
• Lead and other heavy metals create reactive radicals which
damage cell structures including DNA and cell membranes.

• Lead also interferes with DNA transcription & enzymes that help in
the synthesis of vitamin D, and enzymes that maintain the integrity
of the cell membrane.

• Anemia may result when the cell membranes of red blood cells
become more fragile.

• basophilic stippling of the cytoplasm occur due to aggregation of

ribosomes.

• Interfere with erythropoietin production by direct toxic effect on

renal tubules.
The nucleated RBCs contain basophilic stippling of the
cytoplasm. This suggests a toxic injury to the bone
marrow, such as lead poisoning. Such stippling may also
appear with severe anemia, such as a megaloblastic
.anemia
• One of the main causes for the pathology of lead is that it interferes
with the activity of an essential enzyme called delta-aminolevulinic
acid dehydratase (ALAD) which is important in the biosynthesis of
heme.

• Lead interferes with metabolism of bones and teeth and alters the
permeability of blood vessels and collagen synthesis.

• Lead interferes with the release of neurotransmitters which

important in many functions including learning.

• Lead interferes with rennin-angiotensin system & may cause HTN

• Also alter with uric acid excretion resulting in hyperuricemia & gout.
Symptoms
• Symptoms in children

• Abdominal pain
• Vomiting
• Constipation
• Loss of appetite
• Weight loss
• fatigue
• Irritability
• Learning difficulties
• Blue lines on the gums
• Symptoms in adults

• Headache
• Abdominal pain
• High blood pressure
• Memory loss
• Mood disorders
• Declines in mental functioning
• Pain, numbness or tingling of the extremities
• Muscular weakness
• Reduced sperm count, abnormal sperm
• Miscarriage or premature birth in pregnant women
 LEAD
Lines gingiva & long bones
Encephalopathy & RBC basophilic stippling
Abdominal colic & anemia
Drop foot & drop wrist
Complications
• Renal: nephropathy and may cause Fanconi syndrome.

• CVS: high blood pressure, coronary heart disease, heart rate

variability, cardiac autonomic dysfunction and death from stroke.

• Reproductive system: infertility, miscarriage, prematurity & low

birth weight.

• Nervous system: depression and anxiety, learning disabilities &

peripheral neuropathy.
Diagnosis
• Diagnosis from the medical history & clinical signs.

• Blood film examination may reveal basophilic stippling of red

blood cells & iron-deficiency anemia (microcytic
hypochromic).

• measuring erythrocyte protoporphyrin (EP) & lead level in

blood samples.

• If blood lead levels are high but EP is still normal, this finding
suggests exposure was recent.

• Urinary DALA is used as screening test to detect lead

exposure.
• Bony radiography to R/O chronic exposure to lead

• The current reference range for acceptable blood lead

concentrations in healthy persons without excessive exposure
to environmental sources of lead is less than 5 µg/dL for
children.

• It was less than 25 µg/dL for adults.

• And for lead-exposed workers is not more than 40 µg/dL in a

random blood specimen.
Plain abdominal radiograph in a 3-year-old patient shows
multiple metallic particles due to ingested flakes of lead
.paint
Treatment

• The first step in treating all degrees of lead poisoning is to

remove the source of the contamination.

• Treatment of iron, calcium, and zinc deficiencies, which are

associated with increased lead absorption.

• When lead-containing materials are present in the gastrointestinal

tract (as evidenced by abdominal X-rays), whole bowel irrigation,
cathartics, endoscopy, or even surgical removal may be used to
eliminate it from the gut and prevent further exposure.

• If lead encephalopathy is present, anticonvulsants may be given to

control seizures, and treatments to control swelling of the brain by
mannitol.
• Chelation therapy.

• Medication that binds with the lead & excreted it in the urine.

• Cal Na2 EDTA therapy. Calcium disodium ethylene diamine tetraacetic

acid.
• It should be given with calcium to avoid hypocalcemia.

• Dimercaprol (BAL) British anti-lewisite

• Note: both Cal Na2 EDTA & BAL should be given concurrently, as EDTA
mobilize lead from the storage sites to the blood, while BAL combine
with lead in blood to be excreted in urine.

• D-penicillamine.
 Mercury toxicity
• Pure mercury is a liquid metal.

• Mercury is a naturally occurring element that is found in air, water and soil.

• it used to make products like thermometers, barometers & dental amalgam.

Mercury toxicity
•Elemental
It exists in(Liquid)
several forms:
•
Inorganic (Salts) Organic
elemental or metallic
Absorbed by respiratory system mercury,
• inorganic mercury compounds, Absorbed by GIT/kidney )extremely toxic(
and
• organic mercury compounds.
Neurotoxicity Corrosive like effect Hepato/Neurotoxicity
Pathophysiology
• Elemental mercury:

• liquid metallic mercury is poorly absorbed by ingestion and skin

contact.

• Approximately 80% of inhaled mercury vapor is absorbed via the

respiratory tract, where it enters the circulatory system and is
distributed throughout the body.

• Chronic exposure by inhalation, even at low concentrations

leading to tremors, impaired cognitive skills, and sleep
disturbance in workers.
• Acute inhalation of high concentrations causes a wide variety of
cognitive, personality, sensory, and motor disturbances.

• The most prominent symptoms include tremors (initially

affecting the hands and sometimes spreading to other parts of
the body).

• Emotional liability , insomnia, memory loss, neuromuscular

changes (weakness, muscle atrophy, muscle twitching).

• Headaches, polyneuropathy (paresthesia, stocking-glove

sensory loss, hyperactive tendon reflexes, slowed sensory and
motor nerve conduction velocities), and performance deficits in
tests of cognitive function.
 • Inorganic mercury compounds

• Mercury occurs inorganically as salts such as mercury chloride.

• Mercury salts affect primarily the gastrointestinal tract and the

kidneys, and can cause severe kidney damage.

• It cannot cross the blood–brain barrier easily so, no or a little

neurological damage may occur.

• Mercury salts are more toxic because their solubility in water

& its effect on GIT like corrosive .

• They are more readily absorbed from the gastrointestinal tract.

 Organic mercury compounds •

• Compounds of mercury tend to be much more toxic than the

elemental form.

• Organic compounds of mercury are often extremely toxic and

can causing brain and liver damage.

• Organic form are found in antiseptic, bactericidal, fungicides &

insecticidal.

• The most dangerous mercury compound, dimethylmercury, is so

toxic that even a few microliters spilled on the skin can cause
death.
Signs and symptoms
• Common symptoms of mercury poisoning include peripheral neuropathy ,
profuse sweating, tachycardia , increased salivation, and hypertension.

• Skin discoloration (pink cheeks, fingertips and toes), swelling, and

desquamation (shedding of skin).

• Other symptoms may include kidney dysfunction (e.g. Fanconi syndrome) or

neuropsychiatric symptoms such as emotional liability & memory
impairment.
• Affected children may show red cheeks, nose and lips, ashen
gray mucous membrane, loss of hair, teeth, and nails,
transient rashes, hypotonia and increased sensitivity to light,
it's called Acrodynia or Pink disease.
Diagnosis
• Diagnosis of elemental or inorganic mercury poisoning involves
determining the history of exposure, physical findings, and an elevated
body of mercury.

• Whole-blood mercury concentrations are typically less than 6 μg/L.

• If the exposure is chronic, urine levels can be obtained; 24-hour

collections.

• Diagnosis of organic mercury poisoning by hair analysis is more reliable

than urinary mercury levels.

• EDTA is contraindicated because reacting with mercury & cause

nephrotoxic complex.
Treatment
• ABC especially with inhalation of elemental mercury & ingestion of caustic
inorganic mercury, both of which may cause airway obstruction & failure.

• Identifying and removing the source of the mercury .

• Decontamination requires removal of clothes, washing skin with soap and

water, and flushing the eyes with saline solution as needed.

• Chelation therapy for acute inorganic mercury poisoning can be done with
• DMSA, 2,3-dimercapto-1-propanesulfonic acid (DMPS),
• D-penicillamine (DPCN), or
• Dimercaprol (BAL).

• Only DMSA is use in children for treating mercury poisoning.

Arsenic toxicity
• Arsenic and its compounds are poisonous.

• They have been used to make rat poison and some insecticides.

• Arsenic poisoning is a condition caused by the ingestion, or

inhalation of dangerous levels of arsenic.

• Arsenic has no odor & no taste.

signs and symptoms of arsenic
poisoning
• If the arsenic has been ingested orally, the first signs and
symptoms of arsenic poisoning will appear within thirty
minutes, and may include:
• •Drowsiness

• •Headaches

• •Confusion

• •Terrible diarrhea
• if the arsenic has been inhaled, or a less concentrated amount
has been ingested, symptoms may take longer to occur.

• As the arsenic poisoning develops, the patient may start

suffering convulsions and their fingernail pigmentation may
change (leukonychia).

• Arsenic poisoning typically affects the skin, liver, lungs and

kidneys.

• The final stage of the poisoning causes the patient to suffer

seizures and go into shock, this could lead to death.
Signs and Symptoms are associated with severe
:arsenic poisoning

• •Excess salivation
• Excessive sweating
• •Breath smells like garlic
• •Vomiting
• •Diarrhea
• Stomach cramps
• •Problems swallowing
• •Blood in the urine
• •Cramping muscles
• •Loss of hair
• •Convulsions
Complications linked to long-term arsenic
:consumption include

• •Cancer
• •Liver disease
• •Diabetes
• •Nervous system complications - such as loss of sensation in the limbs (peripheral
neuropathy) , hearing problems & digestive difficulties.

• Black Foot disease: it is a peripheral vascular disease due to peripheral vascular

oblitration appearing with acrocynosis, raynauds phenomenon.

• Dermatologic effect: alopecia, hypo-or hyperpigmentation, palmoplantar

keratosis.

• Mee”s lines: transverse white lines in the nails appear several weeks after
mercury exposure.
palmoplantar keratosis
Diagnosis
• Levels of arsenic can be measured by taking blood, hair, urine, and
fingernail samples.

• Treatment:
• Removing clothes that could possibly be contaminated with arsenic
• Washing and rinsing skin that has been affected

• Bowel irrigation - This removes traces of arsenic and prevents it from being
absorbed into the gut.
• Blood transfusion
• Observing kidney function
• Chelation therapy - (dimercaptosuccinic acid & dimercaprol) to isolate the
arsenic from the blood proteins
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